Organ failure due to iron-mediated injury is the leading cause of death in patients with disorders such as thalassemia major that require long-term chronic transfusion. Treatment with the iron chelator, Desferrioxamine, can prevent iron-related morbidity and mortality. Most patients use Desferrioxamine suboptimally, however, due largely to its unwieldy mode of administration, namely continuous subcutaneous infusion over 12 to 24 hours. The investigators will explore the feasibility of using new delivery systems for the drug. Drug delivery will be targeted to the heart and liver, the organs most susceptible to iron-mediated injury. Initial studies of toxicity and efficacy of delivery will be carried out using a rat model system. The concentration of Desferrioxamine will approximate, that needed for clinical efficacy. Subsequent experiments will be performed with iron overloaded thalassemic rats, as well as iron overloaded pigs. This work should lead to an efficacious mode of chelation therapy that is acceptable to patients. In addition, the new delivery method could be used in countries that presently lack the capital resources for the standard Desferrioxamine administration. PROPOSED COMMERCIAL APPLICATION: Alternative approaches to iron chelation therapy and enhancement of targeted drug delivery are of great commercial value. By improving biological half life, tissue targeting ease of administration will result in cost reduction to patients receiving the iron-chelation therapy. The two compounds currently used present a number of clinical problems.